Bottom Line:
Moreover, tau and α-synuclein appear to promote the fibrillization and solubility of each other in vitro and in vivo.This suggests that interactions between tau and α-synuclein form a deleterious feed-forward loop essential for the development and spreading of neurodegeneration.Here, we review the recent literature with respect to elucidating the possible links between α-synuclein and tau.

ABSTRACTThe accumulation of α-synuclein aggregates is the hallmark of Parkinson's disease, and more generally of synucleinopathies. The accumulation of tau aggregates however is classically found in the brains of patients with dementia, and this type of neuropathological feature specifically defines the tauopathies. Nevertheless, in numerous cases α-synuclein positive inclusions are also described in tauopathies and vice versa, suggesting a co-existence or crosstalk of these proteinopathies. Interestingly, α-synuclein and tau share striking common characteristics suggesting that they may work in concord. Tau and α-synuclein are both partially unfolded proteins that can form toxic oligomers and abnormal intracellular aggregates under pathological conditions. Furthermore, mutations in either are responsible for severe dominant familial neurodegeneration. Moreover, tau and α-synuclein appear to promote the fibrillization and solubility of each other in vitro and in vivo. This suggests that interactions between tau and α-synuclein form a deleterious feed-forward loop essential for the development and spreading of neurodegeneration. Here, we review the recent literature with respect to elucidating the possible links between α-synuclein and tau.

Fig1: Overlap of proteinopathies. In numerous neurodegenerative disorders, amyloid deposits composed of α-synuclein protein (red circle), tau protein (blue circle) and Aβ peptide (yellow circle) are found. Histopathological classification of neurodegenerative diseases is based on the nature and localization of these deposits in the nervous system. The pathologies are not hermetically isolated categories but form a continuum and concomitance of αsyn and tau pathology is not rare. αSyn pathology (or synucleinopathy) is not restricted to PD but is a feature of several dementing disorders such as PDD, DLB, and frequently occurs in AD where it contributes to secondary symptoms. By contrast tauopathy is repeatedly observed in numerous disorders primarily classified as synucleinopathies and may contribute to clinical heterogeneity.

Mentions:
Interestingly, at the molecular level, protein misfolding, accumulation, aggregation and subsequently the formation of amyloid deposits are common features in many neurological disorders including AD and PD. Thus neurodegenerative diseases are sometimes referred to as proteinopathies [4]. The existence of a common mechanism suggests that neurodegenerative disorders likely share a common trigger and that the nature of the pathology is determined by the type of the aggregated protein and the localization of the cell affected (Figures 1, 2 and 3).Figure 1

Fig1: Overlap of proteinopathies. In numerous neurodegenerative disorders, amyloid deposits composed of α-synuclein protein (red circle), tau protein (blue circle) and Aβ peptide (yellow circle) are found. Histopathological classification of neurodegenerative diseases is based on the nature and localization of these deposits in the nervous system. The pathologies are not hermetically isolated categories but form a continuum and concomitance of αsyn and tau pathology is not rare. αSyn pathology (or synucleinopathy) is not restricted to PD but is a feature of several dementing disorders such as PDD, DLB, and frequently occurs in AD where it contributes to secondary symptoms. By contrast tauopathy is repeatedly observed in numerous disorders primarily classified as synucleinopathies and may contribute to clinical heterogeneity.

Mentions:
Interestingly, at the molecular level, protein misfolding, accumulation, aggregation and subsequently the formation of amyloid deposits are common features in many neurological disorders including AD and PD. Thus neurodegenerative diseases are sometimes referred to as proteinopathies [4]. The existence of a common mechanism suggests that neurodegenerative disorders likely share a common trigger and that the nature of the pathology is determined by the type of the aggregated protein and the localization of the cell affected (Figures 1, 2 and 3).Figure 1

Bottom Line:
Moreover, tau and α-synuclein appear to promote the fibrillization and solubility of each other in vitro and in vivo.This suggests that interactions between tau and α-synuclein form a deleterious feed-forward loop essential for the development and spreading of neurodegeneration.Here, we review the recent literature with respect to elucidating the possible links between α-synuclein and tau.

ABSTRACTThe accumulation of α-synuclein aggregates is the hallmark of Parkinson's disease, and more generally of synucleinopathies. The accumulation of tau aggregates however is classically found in the brains of patients with dementia, and this type of neuropathological feature specifically defines the tauopathies. Nevertheless, in numerous cases α-synuclein positive inclusions are also described in tauopathies and vice versa, suggesting a co-existence or crosstalk of these proteinopathies. Interestingly, α-synuclein and tau share striking common characteristics suggesting that they may work in concord. Tau and α-synuclein are both partially unfolded proteins that can form toxic oligomers and abnormal intracellular aggregates under pathological conditions. Furthermore, mutations in either are responsible for severe dominant familial neurodegeneration. Moreover, tau and α-synuclein appear to promote the fibrillization and solubility of each other in vitro and in vivo. This suggests that interactions between tau and α-synuclein form a deleterious feed-forward loop essential for the development and spreading of neurodegeneration. Here, we review the recent literature with respect to elucidating the possible links between α-synuclein and tau.